Explanations for the genesis and propagation of cholera pandemics since 1817 have remained elusive. Evolutionary pathogen change is presumed to have been a dominant factor behind the 7th "El Tor" pandemic, but little is known to support this hypothesis for preceding pandemics. The role of anomalous climate in facilitating strain replacements has never been assessed. The question is of relevance to guide the understanding of infectious disease emergence today and in the context of climate change. We investigate the roles of climate and putative strain variation for the 6th cholera pandemic (1899-1923) using newly assembled historical records for climate variables and cholera deaths in provinces of former British India. We compare this historical pandemic with the 7th (El Tor) one and with the temporary emergence of the O139 strain in Bangladesh and globally. With statistical methods for nonlinear time series analysis, we examine the regional synchrony of outbreaks and associations of the disease with regional temperature and rainfall, and with the El Niño Southern Oscillation (ENSO). To establish future expectations and evaluate climate anomalies accompanying historical strain replacements, climate projections are generated with multi-model climate simulations for different 50-year periods. The 6th cholera pandemic featured the striking synchronisation of cholera outbreaks over Bengal during the El Niño event of 1904-07, following the invasion of the Bombay Presidency with a delay of a few years. Accompanying anomalous weather conditions are similar to those related to ENSO during strain replacements and pandemic expansions into Africa and South America in the late 20th century. Rainfall anomalies of 1904-05 at the beginning of the large cholera anomaly fall in the 99th percentile of simulated changes for the regional climate. Evolutionary pathogen change can act synergistically with climatic conditions in the emergence and propagation of cholera strains. Increased climate variability and extremes under global warming provide windows of opportunity for emerging pathogens.